an open-label, phase 2 trial of nanatinostat in combination with valganciclovir in patients with epstein-barr virus-positive (ebv+) relapsed/refractory lymphomas

Conditions: Epstein-Barr Virus Associated Lymphoproliferative Disorder; EBV-Related PTLD; EBV Related Non-Hodgkin's Lymphoma; EBV-Positive DLBCL, NOS; EBV Associated Lymphoma; EBV Related PTCL, NOS

Summary: a phase 2 study to evaluate the efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory ebv-positive lymphomas

patients with ebv-associated lymphomas have inferior outcomes with standard-of-care therapies compared to those with ebv-negative disease. nanatinostat is a selective class i hdac inhibitor which induces ebv lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form. this open-label, multicenter, multinational, single-arm, phase 2 basket study employs a simon's 2-stage design to allow termination of enrollment into cohorts where treatment appears futile, and will include the following cohorts of patients with ebv+ relapsed/refractory lymphomas: 1. ebv+ diffuse large b-cell lymphoma (dlbcl, nos) 2. peripheral t-cell lymphoma (ptcl), including ptcl-nos and aitl 3. post-transplant lymphoproliferative disorder (ptld) 4. ebv+ lymphoproliferative disorders other than the above, including extranodal nk/t-cell lymphoma (enktl) the study was terminated prematurely and did not reach its target enrollment.

Eligibility criteria:
key inclusion criteria: * ebv+ dlbcl, nos and ptcl, nos, and aitl: relapsed/refractory disease following 1 or more prior systemic therapy(ies) with curative intent. * for ebv+ ptld patients: relapsed/refractory disease following 1 prior therapy and must have received at least 1 course of an anti-cd20 immunotherapy. for patients with ebv+ ptld only, age 12 years and older and weighing greater than 40 kg (adolescent, adult, older adult) are allowed * for other ebv+ relapsed/refractory lymphoma: following at least 1 course of an anit-cd20 immunotherapy and at least 1 course of anthracycline-based chemotherapy (unless contraindicated) * no available therapies in the opinion of the investigator * not eligible for high-dose chemotherapy with allogeneic/autologous stem cell transplantation or car-t therapy * measurable disease per cheson 2007 * ecog performance status 0, 1, 2 * adequate bone marrow function key exclusion criteria: * presence or history of cns involvement by lymphoma * systemic anticancer therapy or car-t within 21 days * antibody (anticancer) agents within 28 days * less than 60 days from prior autologous hematopoietic stem cell or solid organ transplant * less than 90 days from prior allogeneic transplant. * daily corticosteroids (≥20 mg of prednisone or equivalent) within week prior to cycle 1 day 1 * inability to take oral medication, malabsorption syndrome or any other gastrointestinal condition (nausea, diarrhea, vomiting) that may impact the absorption of nanatinostat and valganciclovir. * active infection requiring systemic therapy (excluding viral upper respiratory tract infections).

Keywords: ebv positive post-transplant lymphoproliferative disorder (ptld) ebv lymphoma lymphoproliferative disorders epstein-barr virus (ebv) ebv positive t cell lymphoma ebv positive diffuse large b-cell lymphoma (dlbcl) ebv positive peripheral t-cell lymphoma (ptcl) ebv positive ptld in pediatrics